In this one hour and 8-minute video, Dr. Theresa Strong, FPWR’s Director of Research Programs, explores PWS clinical trials that are already underway or enrolling participants.
Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.
Presentation Summary With Timestamps
0:05 Dr. Theresa Strong Presents
0:16 What’s Happening in PWS Research
- As a founder of FPWR, Dr. Strong remembers when the organization started and there were no clinical trials.
- Today, many exciting clinical trials are underway.
- There are many issues that kids with PWS face, and we want as many tools in the toolbox as possible.
0:50 Drug Development Process
- It takes many years to develop a drug.
- There are ways we can speed the process up a bit, for example starting with repurposed drugs rather than brand-new compounds.
- Recruitment can also slow clinical trials.
- But it is important to note that it takes a while because we want to take a stepwise approach that allows us to safely evaluate the drugs in our population.
- The process can take years.
- When we talk about clinical trials, we talk about Phase 1, Phase 2, Phase 3, or Post-Marketing Trials.
1:52 Three Phases of Clinical Trials
- Phase 1 is often done in healthy volunteers, maybe a new compound, the first time it goes into a human.
- It is a small trial and they want to make sure there are no unexpected safety issues.
- Phase 2 trials also tend to be small. In PWS, it would be anywhere from 10-50 individuals. The companies are looking to see if the drug is having any effect.
- Are there unexpected side effects? Phase 2 also looks at different doses to try to get the different doses right and to understand whether the end points, the measures of efficacy, are good for a larger trial.
- Phase 3 trials are sometimes called pivotal trials. They are larger. In PWS, it would usually include 100-200 participants, and it is designed to definitively show that a drug has the desired effect and it has a meaningful impact on the disorder.
- Phase 3 also allows the companies to gain experience in the longer-term administration of the drug.
- It also has an endpoint. The FDA and the company come to an agreement that the drug shows a significant change in a measure everyone agrees to ahead of time.
3:50 What Slows Down Clinical Trials?
- One of the biggest factors that slows clinical trials is recruitment and getting enough participants.
- That is where our community makes a critical difference, so consider enrolling in trials that make sense for you and your family; it’s really the only way these studies are going to get done so we as a community are going to have the tools we need to help our kids reach their full potential.
- It’s important to think about the risks and benefits of clinical trials.
- Benefits:
- You may have early access to a new, potentially effective treatment. For example, many people who enrolled in the DCCR trial have been on DCCR for two or three years, and it will be another year before it’s available, potentially, for the rest of the community.
- Participating in clinical trials can be a really positive experience. It allows you to build a relationship with PWS experts;
- Kids typically get excellent care when they’re in a clinical trial. They are watched closely and that’s a real plus.
- Pharmaceutical companies cover costs for you to travel, so that’s not an out-of-pocket expense.
- In the big picture, it really helps our community get answers about whether a new drug will work for PWS.
- It’s really critical you get to answer the question, “Does it work for my child or not?”
- As a parent, my son got growth hormone relatively early for his age and it was only because other families were willing to enroll in clinical trials of growth hormone.
- Risks/Challenges:
- Trials require a lot of time, and scheduling.
- The drug may not work, and the full risk of the drug might not be known.
- Protections
- There are a lot of protections in place for study participants in clinical trials; the FDA reviews everything before they’ll allow a study to go forward.
- Clinical trial site will review all of the existing data about the safety of a drug and only move forward if they feel comfortable with that at the clinical trial site.
- An institutional review board also looks at clinical trials and reviews them to make sure the potential benefits outweigh the risks.
- In addition, many trials have independent data monitoring boards that will look at the safety issues throughout a trial and they have the power to stop a trial if they feel an issue is going on.
- The FDA can also halt a trial.
- Ultimately, the decision of whether to enroll your child in a specific trial is up to you, and I would never push anyone to enroll in a clinical trial.
- What I will push you a little bit to do is to learn about a clinical trial, so if your child is in the age that is eligible for a clinical trial, I would encourage you to take the steps to really understand if that trial would work for you and your child. That includes speaking to your local doctor and speaking to the study site coordinator to understand what the trial would entail.
- There are a lot of resources on the FPWR website. We try to keep up to date, and update a map of sites as they come online.
- We also have links to the clinical trials that are active in PWS so you can learn more about them.
- We also have a clinical trials alert that you can sign up for to get notifications of new clinical trials as they come online.
9:17 Q&A
- Anything else we should be thinking about to support drug trials?
- Stay aware of trials, sign up for alerts.
- Join the Global PWS Registry.
11:55 Tonix
- Herb Harris, Executive VIP of Translational Medicine at Tonix
- Tonix is conducting a Phase 2 trial using a compound that is a formulation of oxytocin for treatment of hyperphagia and potentially other symptoms of PWS.
- TNX-2900 (potentiated intranasal oxytocin) is an intranasal oxytocin delivery system containing magnesium.
- Challenge is getting oxytocin delivered into the brain.
- In preclinical studies, magnesium was shown to increase the potency of oxytocin by engaging the oxytocin receptor.
- Trial expected to begin enrollment in 2024.
- Primary endpoint is to reduce hyperphagia.
- Looking forward to engaging with PWS community.
- Will begin enrolling older participants and then add younger.
15:09 Aardvark
- ARD-101 is the most bitter tasting chemical described by human beings.
- That’s important because obviously if something tastes bitter you want to spit it out and not ingest it.
- Bitter taste receptors exist the entire way along the intestine and have lots of different effects.
- One major effect is to make you stop eating what you’re eating.
- When the receptors bind to a drug that stimulates the receptor it causes the release of a lot of important gut hormones that may control appetite and inflammation pathways that are impaired in PWS: GLP1, CCK, for example.
- This is an ongoing phase 2 trial focused on safety and finding the right markers to measure to eventually get FDA approval.
- Important safety fact: This drug is not absorbed. More than 99% of it stays in the gut, so there aren’t systemic side effects, just a little bit of gut discomfort during the first day or so of taking the drug.
- Enrolling about a dozen more participants at sites in Stanford in Palo Alto, California, and Children’s Hospital in Colorado.
- Are able to enroll patients from out of state who are willing to travel, and travel expenses are paid by the sponsor.
- Age criteria: 17-65; if you’re an adult, it’s very helpful if your loved one has guardianship papers. If they don’t, a Zoom meeting is required to make sure the person with PWS has the intellectual capacity to meet requirements for providing informed consent for the study.
- HQC score greater than 10 is not challenging for our population, and there is no BMI limit for the study.
- Study/treatment is over four weeks with one visit before the study starts and then four weeks on the drug with an increasing dose of the drug up to a total of now four times the dose that’s already been tested. Increasing dose from 200 mg twice a day to 800 mg twice a day.
- Waiting for approval from FDA to use the drug long term before there will be an open label extension.
- The compound is already used in some detergents and products to ensure that people don’t eat things they shouldn’t eat.
21:38 Neuren
- Jordan Press, Associate Director of Clinical Development and Operations at Neuron Pharmaceuticals.
- Phase 2 study: OPen Label study of NNZ-2591 as a Potential Treatment for PWS.
- Study duration is 21 weeks, with 13 weeks of treatment, open label (all participants will receive active study drug); oral dosing, liquid.
- 5 clinic visits and 12 visits at home, combination of doctor and nursing visits.
- Study will evaluate safety and pharmacokinetics, how the drug is distributed throughout the body.
- It will also evaluate the clinical response to the drug, behavioral outcomes, and potential biomarkers.
- Optimistic that the study will help to inform a phase 3 design, and if they get to the phase 3 they will be opening an open level extension as a separate study in tandem to that phase 3, and everyone who’s participating in phase 2 can roll over into that open level extension.
- A number of sites, and the one that is currently open is the Rare Disease Research in Atlanta, Georgia.
- Criteria:
- Males and females, 4-12 years.
- Diagnosis of PWS with confirmed genetic etiology.
- Body weight at screening 16.5-220.5 lbs.
- Able to swallow liquid medication.
- Stable seizure profile and treatment regimen
- Participants will need to do assessments, review of current meds, and a medical history at screening to determine eligibility.
- Study broken down into two groups, older and younger, enrolling older group (8-12) first.
- Check clinicaltrials.gov.
26:25 Gideon Richter:KITE-PWS
- Gideon Richter focuses on medications for the central nervous system, and is very focused on PWS.
- Have a phase 2 study to learn about an experimental drug called RGH-707 to address hyperphagia in people with PWS.
- RGH-706 blocks the MCHR-1, which may reduce hyperphagia.
- Enrolling patients for the A part, taking capsules orally, once a day.
- Study duration is 23 weeks with 6 in-person clinical visits.
- Locations in San Diego, Chicago, Cleveland, New York.
- Eligibility criteria:
- 17 years and older.
- Consistent caregiver.
- Genetic diagnosis.
- No GLP in the past 6 months.
- Travel cost and staying on the site is covered.
- Part B will investigate 3 different doses of the compound.
30:16 Harmony Biosciences-Tempo Study
- Tempo Study is a phase 3 efficacy and safety study of Pitolisant in patients with PWS.
- It will compare the efficacy of Pitolisant compared to a placebo and its impact on excessive daytime sleepiness and irritability as well as the effect of the drug on hyperphagia.
- Study participants will take an oral tablet of Pitilosant once a day.
- Study duration: up to a 450day screening/baseline period, an 11-week double blind treatment period, and an optional open-label extension.
- It involves 4 in-person clinic visits.
- Locations around the globe will be announced.
- Criteria:
- 6 years or older.
- PWS diagnosis.
- Have excessive daytime sleepiness.
33:41 Acadia Pharmaceuticals: Carbetocin Nasal Spray for Hyperphagia in PWS
- Setting up a double-blind study in the US of Carbetocin Nasal Spray.
- Phase 3 study of nasal spray 3x a day.
- Half the people will have Carbetocin and the other half placebo.
- Carbetocin is similar to the natural hormone oxytocin.
- FDA recommended an additional study to confirm the efficacy of this low dose.
- 12-week study has 5 in-person clinical visits with locations in the US and Canada.
- Criteria:
- 5-30 years old
- Increased appetite with decreased satiety accompanied by food seeking.
- Lives with caregivers who will complete questionnaires.
- There was a previous phase 3 study by Levo Therapeutics where they studied a high dose and a low dose.
- The low dose worked, but the high dose didn’t. So the FDA asked for more data about the lower dose.
- Acadia felt encouraged by the data.
- Drug is the same formulation, which needs to be refrigerated in the home, frozen in the study.
37:13 VNS4PWS
- Study is owned by the community.
- VNS4PWS: Vagus Nerve Stimulation for Temper Outbursts.
- Study will evaluate the effectiveness of a wearable medical device in treating temper outbursts and disruptive behaviors. It’s a tiny electrode that is attached to a device that looks like a pager.
- The device stimulates a very important branch of the vagus nerve. As opposed to many of the nerves that cause anxiety, the vagus nerve supplies the parasympathetic nervous system, which calms things down, helps us not act on impulse.
- Novel way of stimulating the parasympathetic nervous system.
- Has been shown to be effective in a small study, and they are very excited about testing it out in a larger way.
- Study duration is 12 months, with 2 in-person clinical visits.
- 12 study site locations are pending across the US.
- Eligibility:
- Ages 10-40.
- History of temper tantrums over the past 6 months.
- Stable medications for the past 90 days.
- Study is not going to include individuals under 10 because they may not be able to tolerate leaving on a device for that long.
- Important to note that the device has not been shown to have any significant side effects, and vagal nerve stimulation is a commonly used method to improve other methods such as seizures.
42:20 Light Therapy for Excessive Daytime Sleepiness in PWS
- Trial will evaluate the effectiveness of light therapy on the reduction of excessive daytime sleepiness (EDS).
- Participants will receive either 30 minutes of light therapy or placebo lamp therapy in the mornings and 30 minutes in the afternoon, daily for 3 weeks.
- All visits are remote.
- All participants will be given the option to continue in an open-label extension for an additional 3 weeks.
- We know that light therapy works for patients with depression, for patients with Alzheimer’s, and for people with Parkinson’s Disease.
- Note that there is no travel required, so participants won’t lose sleep traveling across time zones.
- Requires two weeks of pre-screening to keep close account of how sleep has been and that participants meet the requirements of the study.
- People who meet the criteria will be shipped the device and a Fitbit.
- The two devices look the same but work slightly differently; one is effective, and one is the placebo.
- If your child has sleepiness for any cause, they will likely qualify for the study.
- Contact them to find out more about the study.
47:29 Q & A
